Parsey Ramin V, Oquendo Maria A, Simpson Norman R, Ogden R Todd, Van Heertum Ronald, Arango Victoria, Mann J John
Division of Neuroscience, Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
Brain Res. 2002 Nov 8;954(2):173-82. doi: 10.1016/s0006-8993(02)03243-2.
Serotonin (5-HT) 1A receptors have been implicated in a variety of conditions including, depression, suicidal behavior, and aggression. Post-mortem brain studies and in vivo imaging studies report a variety of age and sex effects on brain 5-HT(1A) binding. Behavioral data from 5-HT(1A) specific pharmacological challenges suggest a role for 5-HT(1A) receptors in aggression. The goal of the present study was to determine age, sex, and severity of life-time aggression effects on 5-HT(1A) binding potential (BP) in vivo using positron emission tomography (PET) and the high affinity 5-HT(1A) antagonist, [carbonyl-C-11]WAY-100635 in 12 healthy females (ages 41.0+/-15.7 years) and 13 healthy males (ages 39.6+/-15.5 years). Regions of interest included the dorsal raphe, anterior cingulate cortex, cingulate body, hippocampus, amygdala, medial prefrontal cortex (PFC), and orbital PFC. No significant correlation between age and BP was detected in any brain region. MANOVA of the first three principle components demonstrated a significantly higher BP in females compared with males (P=0.0127). Post-hoc tests confirmed sex differences (P<0.05) in the following regions: dorsal raphe, amygdala, anterior cingulate, cingulate body, medial PFC, and orbital PFC. The cerebellar volume of distribution was also significantly higher in females. There is a significant negative correlation between binding in several regions and lifetime aggression. We have replicated our post-mortem finding of higher 5-HT(1A) binding in females compared to males. We did not detect an age dependent decrease in binding in males or females. Lower 5-HT(1A) binding in more aggressive individuals is consistent with pharmacological challenge studies. Future studies should determine whether the binding is a state or trait effect.
血清素（5-羟色胺，5-HT）1A受体与多种病症有关，包括抑郁症、自杀行为和攻击行为。尸检脑研究和体内成像研究报告了年龄和性别对脑5-HT（1A）结合的多种影响。来自5-HT（1A）特异性药理学激发试验的行为数据表明5-HT（1A）受体在攻击行为中起作用。本研究的目的是使用正电子发射断层扫描（PET）和高亲和力5-HT（1A）拮抗剂[羰基-C-11]WAY-100635，在12名健康女性（年龄41.0±15.7岁）和13名健康男性（年龄39.6±15.5岁）中，确定年龄、性别和终生攻击行为的严重程度对体内5-HT（1A）结合潜能（BP）的影响。感兴趣的区域包括中缝背核、前扣带回皮质、扣带回、海马体、杏仁核、内侧前额叶皮质（PFC）和眶额PFC。在任何脑区均未检测到年龄与BP之间的显著相关性。对前三个主成分进行的多变量方差分析表明，女性的BP显著高于男性（P=0.0127）。事后检验证实了以下区域存在性别差异（P<0.05）：中缝背核、杏仁核、前扣带回、扣带回、内侧PFC和眶额PFC。女性的小脑分布容积也显著更高。几个区域的结合与终生攻击行为之间存在显著负相关。我们重复了尸检结果，即女性的5-HT（1A）结合高于男性。我们未检测到男性或女性的结合随年龄增长而降低。攻击性更强的个体中较低的5-HT（1A）结合与药理学激发试验研究结果一致。未来的研究应确定这种结合是一种状态效应还是特质效应。
